Biology subjects

Ci, W.

Publications and source records attributed to Ci, W..

3 recordsLinked to original sources

bioRxiv2026

Single-cell atlas of pig-to-monkey kidney xenotransplantation reveals macrophage chimerism and an IFN-ε orchestrated graft protective immune niche

The clinical translation of xenotransplantation is constrained by an incomplete understanding of the cellular circuitry governing graft rejection versus adaptation under current immunosuppressive regimens. Here, we present a high-resolution single-cell atlas of pig-to-monkey kidney xenotransplantation in a preclinical model, capturing the early immune dynamics preceding graft loss. Our analysis reveals a landscape dominated by innate immunity, characterized by species-specific distribution of macrophages. We identify recipient-derived macrophage subsets (ACKR1+, FN1+, MARCO+, IDO1+) enriched for multiple immune checkpoint molecules, alongside donor-resident subpopulations (APOE+, CCL2+, IL-1A+) exhibiting pro-inflammatory pathogenic signatures, and leverage their transcriptional profiles to computationally predict candidate therapies (belatacept, abatacept, pexidartinib). Further analysis demonstrates that despite divergent differentiation trajectories, both recipient-derived and donor-resident macrophages converge toward hybrid M1/M2 states at their terminal stages. Notably, we uncover a graft-protective circuit orchestrated by epithelial-derived interferon-epsilon (IFN-{varepsilon}), which specifically engages multiple subsets including IDO1+ macrophages to establish a localized immune-tolerant niche. This study establishes the xenograft epithelium as an active participant in immune modulation via the IFN-{varepsilon} axis and reveals macrophage functional chimerism as a key actionable feature of cross-species immune responses.

genomics↗

bioRxiv2019

Mutational signatures in upper tract urothelial carcinoma define etiologically distinct subtypes with prognostic relevance

Parts of East Asia have a very high upper tract urothelial carcinoma (UTUC) prevalence, and an etiological link between the medicinal use of herbs containing aristolochic acid (AA) and UTUC has been established. The mutational signature of AA, which is characterized by a particular pattern of A:T to T:A transversions, can be detected by genome sequencing. Thus, integrating mutational signatures analysis with clinicopathological data may be a crucial step toward personalized treatment strategies for the disease. Therefore, we performed whole-genome sequencing (WGS) of 90 UTUC patients from China. Mutational signature analysis via nonnegative matrix factorization method defined three etiologically distinct subtypes with prognostic relevance: (i) AA, the typical AA mutational signature characterized by signature 22, had the highest tumor mutation burden, the best clinical outcomes; (ii) Age, an age-related group featured by signatures 1 and 5, had the lowest weighted genome instability index score, the worst clinical outcomes; and (iii) DSB, signature with deficiencies in DNA double strand break-repair featured by signatures 3, the intermediate clinical outcomes. Additionally, the distinct AA subtype was associated with AA exposure, the highest number of predicted neoantigens and heavier lymphocytes infiltrating. Thus, it may be good candidate for immune checkpoint blockade therapy. Notably, we showed AA-mutational signature was also identified in histologically \"normal\" urothelial cells. Thus, non-invasive urine test based on the AA-mutational signature could take advantage of this \"field effect\" to screen individuals at increased risk of recurrence due to exposure to herbal remedies containing the carcinogen AA. Collectively, the findings here may accelerate the development of novel prognostic markers and personalized therapeutic approaches for UTUC patients in China.

genomics↗

bioRxiv2017

Identification of methylation and hydroxymethylation haplotype blocks as distal regulatory elements aids in deconvolution of heterogeneous brain tissues

5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in the mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC, respectively, at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently had 5mC modification simultaneously and enriched in gene body regions of neuron development related genes in brain tissues. These results supported a prominent role of oxidizing 5mC to 5hmC as new epigenetic mark. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions which further supported that oxidized 5mC to 5hmC co-ordinately in a subset of cells within heterogeneous brain tissues. Consistently, using a metric called methylation haplotype load, we defined a subset of 1,361 tissue-specific MHBs and 3,818 shared MHBs which were predominantly regulatory elements, and aids in deconvolution of heterogeneous brain tissues. Our results provide new insights into the role of co-ordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.

genetics↗